Hot and Cold Theory: A Personalized Medicine Approach.

The hot and cold theory is an important part of Traditional Medicines (TMs) which can be used in health care, disease prevention, diagnosis, and treatment purposes. However, little has been said about the material basis of the theory and how the hot and cold theory can be integrated with the conventional medicine. This article will summarize how the Hot and Cold Theory may help health care providers to personalize their treatment, as well as the material basis of the theory and its future prospects.

[Molecular mechanism of Fagopyri Dibotryis Rhizoma in treatment of acute lung injury based on network pharmacology and in vitro experiments].

The present study explored the mechanism of Fagopyri Dibotryis Rhizoma(FDR) and its main active components in the treatment of acute lung injury(ALI) based on the network pharmacology and the in vitro experiments. The main active components of FDR were obtained from the TCMSP database and screened by oral bioavailability and drug-likeness. The related target proteins of FDR were retrieved from the PubChem database, and the target genes related to ALI were screened out from the GeneCards database. A protein-protein interaction(PPI) network of compound target proteins and ALI target genes was constructed using STRING 11.0. Ingenuity Pathway Analysis(IPA) platform was used to analyze the common pathways of the potential compound target proteins of FDR and ALI target genes, thereby predicting the key targets and potential signaling pathways of FDR for the treatment of ALI. Finally, the potential pathways and key targets were verified by the in vitro experiments of lipopolysaccharide-induced RAW264.7 cells intervened by epicatechin(EC), the active component of FDR. The results of network pharmacology showed that 15 potential active components such as EC, procyanidin B1, and luteolin presumedly functioned in the treatment of ALI through nuclear transcription factor-κB(NF-κB) signaling pathway, transforming growth factor-ß(TGF-ß) signaling pathway, and adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway through key targets, such as RELA(P65). The results of in vitro experiments showed that 25 µmol·L~(-1) EC had no toxicity to cells and could inhibit the expression of the p65-phosphorylated protein in the NF-κB signaling pathway to down-regulate the expression of downstream inflammatory cytokines, including tumor necrosis factor-α(TNF-α), IL-1ß and nitric oxide(NO), and up-regulate the expression of IL-10. These results suggested that the therapeutic efficacy of FDR on ALI was achieved by inhibiting the phosphorylation of p65 protein in the NF-κB signaling pathway and down-regulating the level of proinflammatory cytokines downstream of the signaling pathways.

Association between early treatment with Qingfei Paidu decoction and favorable clinical outcomes in patients with COVID-19: A retrospective multicenter cohort study.

The coronavirus disease 2019 (COVID-19) epidemic has been almost controlled in China under a series of policies, including "early diagnosis and early treatment". This study aimed to explore the association between early treatment with Qingfei Paidu decoction (QFPDD) and favorable clinical outcomes. In this retrospective multicenter study, we included 782 patients (males, 56 %; median age 46) with confirmed COVID-19 from 54 hospitals in nine provinces of China, who were divided into four groups according to the treatment initiation time from the first date of onset of symptoms to the date of starting treatment with QFPDD. The primary outcome was time to recovery; days of viral shedding, duration of hospital stay, and course of the disease were also analyzed. Compared with treatment initiated after 3 weeks, early treatment with QFPDD after less than 1 week, 1-2 weeks, or 2-3 weeks had a higher likelihood of recovery, with adjusted hazard ratio (HR) (95 % confidence interval [CI]) of 3.81 (2.65-5.48), 2.63 (1.86-3.73), and 1.92 (1.34-2.75), respectively. The median course of the disease decreased from 34 days to 24 days, 21 days, and 18 days when treatment was administered early by a week (P < 0.0001). Treatment within a week was related to a decrease by 1-4 days in the median duration of hospital stay compared with late treatment (P<0.0001). In conclusion, early treatment with QFPDD may serve as an effective strategy in controlling the epidemic, as early treatment with QFPDD was associated with favorable outcomes, including faster recovery, shorter time to viral shedding, and a shorter duration of hospital stay. However, further multicenter, prospective studies with a larger sample size should be conducted to confirm the benefits of early treatment with QFPDD.

[Retracted] Chronic oxymatrine treatment induces resistance and epithelial­mesenchymal transition through targeting the long non­coding RNA MALAT1 in colorectal cancer cells.

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the cell migration and invasion assay data featured in Figs. 2B, 5C, 6B and C were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been submitted elsewhere prior to the submission of this paper to Oncology Reports, or were under consideration for publication at around the same time (one of which has been retracted). In view of the fact that certain of these data had already apparently been submitted for publication prior to the submission of this article to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 39: 967­976, 2018; DOI: 10.3892/or.2018.6204].

Strictosamide ameliorates LPS-induced acute lung injury by targeting ERK2 and mediating NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) ranks among the deadliest pulmonary diseases, significantly impacting mortality and morbidity. Presently, the primary treatment for ALI involves supportive therapy; however, its efficacy remains unsatisfactory. Strictosamide (STR), an indole alkaloid found in the Chinese herbal medicine Nauclea officinalis (Pierre ex Pit.) Merr. & Chun (Wutan), has been found to exhibit numerous pharmacological properties, particularly anti-inflammatory effects. AIM OF THE STUDY: This study aimes to systematically identify and validate the specific binding proteins targeted by STR and elucidate its anti-inflammatory mechanism in lipopolysaccharide (LPS)-induced ALI. MATERIALS AND METHODS: Biotin chemical modification, protein microarray analysis and network pharmacology were conducted to screen for potential STR-binding proteins. The binding affinity was assessed through surface plasmon resonance (SPR), cellular thermal shift assay (CETSA) and molecular docking, and the anti-inflammatory mechanism of STR in ALI treatment was assessed through in vivo and in vitro experiments. RESULTS: Biotin chemical modification, protein microarray and network pharmacology identified extracellular-signal-regulated kinase 2 (ERK2) as the most important binding proteins among 276 candidate STR-interacting proteins and nuclear factor-kappaB (NF-κB) pathway was one of the main inflammatory signal transduction pathways. Using SPR, CETSA, and molecular docking, we confirmed STR's affinity for ERK2. In vitro and in vivo experiments demonstrated that STR mitigated inflammation by targeting ERK2 to modulate the NF-κB signaling pathway in LPS-induced ALI. CONCLUSIONS: Our findings indicate that STR can inhibit the NF-κB signaling pathway to attenuate LPS-induced inflammation by targeting ERK2 and decreasing phosphorylation of ERK2, which could be a novel strategy for treating ALI.

Infection with SARS-CoV-2 can cause pancreatic impairment.

Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of diabetes. Herein, we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates (NHPs) models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 patients. Multi-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and humans. Minor and limited phenotypic and histopathological changes were observed in adult models. Systemic proteomics and metabolomics results indicated metabolic disorders, mainly enriched in insulin resistance pathways, in infected adult NHPs, along with elevated fasting C-peptide and C-peptide/glucose ratio levels. Furthermore, in elder COVID-19 NHPs, SARS-CoV-2 infection causes loss of beta (ß) cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis, activation of α-SMA and aggravated fibrosis consisting of lower collagen in serum, an increase of pancreatic inflammation and stress markers, ICAM-1 and G3BP1, along with more severe glycometabolic dysfunction. In contrast, vaccination maintained glucose homeostasis by activating insulin receptor α and insulin receptor ß. Overall, the cumulative risk of diabetes post-COVID-19 is closely tied to age, suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.

The effect of Huashibaidu formula on the blood oxygen saturation status of severe COVID-19: A retrospective cohort study.

BACKGROUND: Huashibaidu Formula (HSBD) for the COVID-19 treatment has been supported by the China's Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia. However, it is not clear whether HSBD can improve blood oxygen saturation and when it should be used with conventional therapies. PURPOSE: To access the effect of HSBD combined with conventional treatment on blood oxygen saturation of COVID-19 patients. METHODS: A single-center retrospective cohort study was conducted to collect the confirmed severe COVID-19 patients' information, treated by the National Traditional Chinese Medicine Medical Team at the Jinyintan hospital between January 24 and March 31, 2020. According to whether HSBD was used during hospitalization, participants were separated into the conventional treatment group and the HSBD group (HSBD and conventional treatment). The primary observation indicators included the time for relieving blood oxygen saturation and the improvement ratio of blood oxygen saturation in each group. RESULTS: Of 111 patients with severe COVID-19, 53.2% (59/111) received HSBD, and 46.8% (52/111) only received conventional treatment, respectively. No statistically significant difference was found in image, clinical symptoms, and past medical history between the two groups (p > 0.05). Notably, the median time for relieving blood oxygen saturation in the conventional treatment group was 11 days (IQR, 8-14.25), while that in the HSBD group was only 6 days (IQR, 3.25-10.75), which was significantly shortened by 4.09 days (95%CI, 2.07-6.13; p= 0.0001), compared with the conventional treatment group. After repeated measurement design analysis, the main effect within times (p< 0.001) and the main effect were significantly different under the oxygen saturation dimension between two groups (p= 0.004). However, time and group interaction were observed no significant difference (p= 0.094). After 14 days of treatment, the improvement ratio of the HSBD group over the conventional treatment group was 1.20 (95%CI, 0.89-1.61). CONCLUSION: For severe COVID-19 patients, the HSBD has a tendency to shorten the time for relieving blood oxygen saturation. After taking a course of HSBD, the effect can be more obvious.

Traditional Chinese Medicine in Treating Children With Coronavirus Disease 2019: A Scoping Review.

Coronavirus disease 2019 (COVID-19) is currently widely spread across the world. Traditional Chinese Medicine (TCM) plays an important role in the overall treatment process. As a special group of population, the treatment outcome of children with COVID-19 has attracted much attention. Our study summarizes the current situation of TCM treatment of children with COVID-19. The results showed that TCM displayed a positive role in the treatment process, and that no significant adverse reactions were found. Our findings provide analytical evidence for the efficacy and safety of TCM participation in the treatment of COVID-19 in children.

Clinical Efficacy and Safety of Chinese Patent Medicine Combined with Oseltamivir for the Treatment of Adult Influenza: A Systematic Review and Meta-Analysis.

Influenza is a sudden and serious viral breathing and lung-related infectious disease that causes significant deadliness and death worldwide. Now, the international treatment is oseltamivir. Chinese patent medicine (CPM) as a kind of different therapy is used in the treatment of influenza in China. The aim of this study was to interpret the clinical efficacy and safety of CPM combined with oseltamivir in the treatment of adult influenza by reviewing all relevant randomized controlled trials, and to provide new ideas and methods for the treatment of influenza. PubMed, Embase, Cochrane Library, SinoMed, CNKI, and Wanfang Database were searched from the date of beginning until 1 June 2021, for the references on treatment of influenza with CPM. According to standard information extraction tables, two people worked to find and aggregate information independently. Review Manager 5.2 was used to study data carefully and evaluate risk of bias. A total of nine trials of 906 patients were included. Based on the meta-analysis, compared to oseltamivir, CPM combined with oseltamivir had better effect in the time of defervescence [MD = -17.68, 95% CI (-25.93, -9.44), P < 0.0001], the time of symptom improvement [MD = -22.28, 95% CI (-26.77, -17.80), P < 0.00001], and the time of hospitalization [MD = -2.04, 95% CI (-3.45, -0.63), P = 0.005]. Related to safety [RR = 0.69, 95% CI (0.38, 1.23), P = 0.21], the experimental group had fewer adverse reactions than the control group, but there is no statistical significance. The findings show that CPM combined with oseltamivir in adult influenza has a better efficacy in shortening the time of defervescence and symptom improvement, reducing the time of hospitalization. However, publication bias is inevitable due to the low methodological quality check of the clinical research about diagnostic criteria, definition of adult influenza, and small number of articles, and further large sample sizes and multi-center clinical trials are needed to give better proof for its efficacy and safety.

Comparing different machine learning techniques for predicting COVID-19 severity.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is still ongoing spreading globally, machine learning techniques were used in disease diagnosis and to predict treatment outcomes, which showed favorable performance. The present study aims to predict COVID-19 severity at admission by different machine learning techniques including random forest (RF), support vector machine (SVM), and logistic regression (LR). Feature importance to COVID-19 severity were further identified. METHODS: A retrospective design was adopted in the JinYinTan Hospital from January 26 to March 28, 2020, eighty-six demographic, clinical, and laboratory features were selected with LassoCV method, Spearman's rank correlation, experts' opinions, and literature evaluation. RF, SVM, and LR were performed to predict severe COVID-19, the performance of the models was compared by the area under curve (AUC). Additionally, feature importance to COVID-19 severity were analyzed by the best performance model. RESULTS: A total of 287 patients were enrolled with 36.6% severe cases and 63.4% non-severe cases. The median age was 60.0 years (interquartile range: 49.0-68.0 years). Three models were established using 23 features including 1 clinical, 1 chest computed tomography (CT) and 21 laboratory features. Among three models, RF yielded better overall performance with the highest AUC of 0.970 than SVM of 0.948 and LR of 0.928, RF also achieved a favorable sensitivity of 96.7%, specificity of 69.5%, and accuracy of 84.5%. SVM had sensitivity of 93.9%, specificity of 79.0%, and accuracy of 88.5%. LR also achieved a favorable sensitivity of 92.3%, specificity of 72.3%, and accuracy of 85.2%. Additionally, chest-CT had highest importance to illness severity, and the following features were neutrophil to lymphocyte ratio, lactate dehydrogenase, and D-dimer, respectively. CONCLUSIONS: Our results indicated that RF could be a useful predictive tool to identify patients with severe COVID-19, which may facilitate effective care and further optimize resources.

Anti-inflammatory effects of Chaishi Tuire Granules on influenza A treatment by mediating TRAF6/MAPK14 axis.

Objectives: Influenza is an infectious respiratory disease that can cause severe inflammatory reactions and threaten human life. Chaishi Tuire Granules (CSTRG), a Chinese patent medicine widely used clinically in the treatment of respiratory diseases in China, has a definite anti-inflammatory effect. However, the mechanism of CSTRG in the treatment of influenza is still unclear. This study aimed to demonstrate the anti-inflammatory effect of CSTRG on influenza A treatment and potential mechanisms. Methods: Influenza-associated mice pneumonia model was used to explore the antiviral and anti-inflammatory effects of CSTRG in vivo. Bioinformatics analysis methods such as network pharmacology and molecular docking were carried out to predict the main active components and potential anti-inflammatory targets of CSTRG. The anti-inflammatory activity of CSTRG was determined using the lipopolysaccharide (LPS)-induced macrophages RAW264.7 cells in vitro. Results: In vivo results showed that CSTRG can reduce the viral load in the lung tissue of infected mice, reduce the expression of TNF-α and IL-6 in lung tissue and serum, and regulate the host inflammatory response. Additionally, CSTRG treatment markedly improves the sick signs, weight loss, lung index, and lung pathological changes. Bioinformatics analysis predicted that six active compounds of CSTRG including quercetin, kaempferol, luteolin, beta-sitosterol, sitosterol, and stigmasterol could contribute to the anti-influenza activity through regulating the TRAF6/MAPK14 axis. The following research confirmed that CSTRG significantly inhibited pro-inflammatory cytokines (TNF-α and IL-6) by suppressing the expression of TRAF6 and MAPK14 in LPS-stimulated macrophages RAW264.7 cells. Conclusion: CSTRG might inhibit the inflammatory response by mediating the TRAF6/MAPK14 axis. In the future, in-depth research is still needed to verify the mechanism of CSTRG in the treatment of influenza.

Efficacy and Safety of Chinese Patent Medicine Combined With Oseltamivir in Treatment of Children With Influenza: A meta-Analysis.

Background: Recently, Chinese patent medicines (CPMs) have been widely used to treat children with influenza in China, with curative effects. Therefore, the efficacy and safety of such treatment require further evaluation. The present meta-analysis integrated data from several independent studies to determine overall treatment trends in children with influenza. Methods: The following databases were searched for randomized controlled trials (RCTs) published from their inception to December 12, 2020: CNKI, Wanfang, SinoMed, PubMed, Cochrane library, and Embase. Two researchers independently extracted the data, assessed the methodological quality of the studies, and conducted a meta-analysis of the results using Review Manager 5.2. The results were assessed using forest plots, and publication bias was evaluated using a funnel plot. Results: A total of 21 RCTs involving 2960 cases were included. Compared to oseltamivir alone, CPMs combined with oseltamivir reduced the duration of symptoms, including that of fever (mean difference [MD] = -0.64, 95% confidence interval [CI]: -0.86 to -0.41, P < 0.00001), cough (MD = -0.82, 95% CI: -1.02 to -0.62, P < 0.00001), nasal obstruction (MD = -0.88, 95% CI: -1.15 to -0.61, P < 0.00001), and sore throat (MD = -0.92, 95% CI: -1.26 to -0.57, P < 0.00001). Combined therapy also reduced the time of viral shedding (MD = -0.53, 95% CI: -0.70 to -0.36, P < 0.00001) and the occurrence of adverse drug reactions (ADRs) (RR=0.53, 95% CI: 0.34 to 0.83, P = 0.005). Conclusions: CPMs combined with oseltamivir reduced the duration of symptoms, shortened the time of viral shedding, and reduced the number of ADRs. However, these results should be considered with caution because there was marked heterogeneity and publication bias in the research data. More rigorous RCTs should be designed to verify the effect of CPMs in children with influenza.

YYFZBJS inhibits colorectal tumorigenesis by remodeling gut microbiota and influence on M2 macrophage polarization in vivo and in vitro.

Our previous studies indicated that the extract of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) had potent anticancer activities by significantly inhibiting intestinal tumor development in ApcMin/+ mice. However, knowledge regarding the mechanism and effect of YYFZBJS in the prevention of colorectal cancer is limited. In this study, we aim to investigate the preventive effects of YYFZBJS in enterotoxigenic Bacteroides fragilis (ETBF)-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis. First, the colonic tissues of the AOM/DSS mouse models were collected for biomedical analysis, and gut microbiota profiling was detected post YYFZBJS treatment using a 16S rRNA gene sequencing. Then, antibiotic solution (Abx) mice were acclimated with AOM/DSS treatment and then fed with ETBF with or without YYFZBJS for three cycles. As expected, the intragastric administration of YYFZBJS in the AOM/DSS mouse model significantly decreased the tumor load, the severity of disease activity index (DAI) scores, and the level of M2 macrophage markers such as CD206, Arg-1 and IL-10. Notably, the reverse of polarized macrophages induced by YYFZBJS could suppress CRC cell proliferation and infiltration, as demonstrated by the decrease of some tumor proliferation-related proteins in a dose-dependent manner. Importantly, ETBF dysbiosis can contribute to colon tumor development by stimulating p-STAT3 mediated M2 macrophages polarization to promote chronic inflammation and adenoma malignant transformation, which YYFZBJS can effectively limit. Altogether, we demonstrate that ETBF dysbiosis may contribute to M2 macrophages-promoted colon carcinogenesis and progression of CRC cells, while YYFZBJS could be a promising protective agent against ETBF-mediated colorectal cancer.

Efficacy and safety of Chinese herbal medicine versus Lopinavir-Ritonavir in adult patients with coronavirus disease 2019: A non-randomized controlled trial.

BACKGROUND: Treatments for coronavirus disease 2019 (COVID-19) are limited by suboptimal efficacy. METHODS: From January 30, 2020 to March 23, 2020, we conducted a non-randomised controlled trial, in which all adult patients with laboratory-confirmed COVID-19 were assigned to three groups non-randomly and given supportive treatments: Group A, Lopinavir-Ritonavir; Group B, Huashi Baidu Formula (a Chinese medicineformula made by the China Academy of Chinese Medical Sciences to treat COVID-19, which is now in the clinical trial period) and Lopinavir-Ritonavir; and Group C, Huashi Baidu Formula. The use of antibiotics, antiviruses, and corticosteroids was permitted in Group A and B. Traditional Chinese medicine injections were permitted in Group C. The primary outcomes were clinical remission time (interval from admission to the first time the patient tested negatively for novel coronavirus or an obvious improvement was observed from chest CT) and clinical remission rate (number of patients whose clinical time was within 16 days/total number of patients). RESULTS: A total of 60 adult patients with COVID-19 were enrolled at sites in Wuhan, China, and the sample size of each group was 20. In Groups A, B and C, the clinical remission rates were 95.0%%(19/20), 100.0%%(20/20) and 100.0%%(20/20), respectively. Compared with Groups A and B, the clinical remission time of Group C was significantly shorter (5.9 days vs. 10.8 days, p < 0.05; 5.9 days vs. 9.7 days, p < 0.05). There was no significant difference among Groups A, B, and C in terms of the time taken to be released from quarantine. The clinical biochemical indicators and safety indexes showed no significant differences among the three groups. CONCLUSIONS: Our findings suggest that Lopinavir-Ritonavir has some efficacy in the treatment of COVID-19, and the Huashi Baidu Formula might enhance this effect to an extent. In addition, superiority was displayed in the treatment of COVID-19 through a combination of the Huashi Baidu Formula and traditional Chinese medicine injection. In future, well-designed prospective double-blinded randomised control trials are required to confirm our findings.

Chinese Medicine Formula Huashibaidu Granule Early Treatment for Mild COVID-19 Patients: An Unblinded, Cluster-Randomized Clinical Trial.

Background: Previous research suggested that Chinese Medicine (CM) Formula Huashibaidu granule might shorten the disease course in coronavirus disease 2019 (COVID-19) patients. This research aimed to investigate the early treatment effect of Huashibaidu granule in well-managed patients with mild COVID-19. Methods: An unblinded cluster-randomized clinical trial was conducted at the Dongxihu FangCang hospital. Two cabins were randomly allocated to a CM or control group, with 204 mild COVID-19 participants in each cabin. All participants received conventional treatment over a 7 day period, while the ones in CM group were additionally given Huashibaidu granule 10 g twice daily. Participants were followed up to their clinical endpoint. The primary outcome was worsening symptoms before the clinical endpoint. The secondary outcomes were cure and discharge before the clinical endpoint and alleviation of composite symptoms after the 7 days of treatment. Results: All 408 participants were followed up to their clinical endpoint and included in statistical analysis. Baseline characteristics were comparable between the two groups (P > 0.05). The number of worsening patients in the CM group was 5 (2.5%), and that in the control group was 16 (7.8%) with a significant difference between groups (P = 0.014). Eight foreseeable mild adverse events occurred without statistical difference between groups (P = 0.151). Conclusion: Seven days of early treatment with Huashibaidu granule reduced the likelihood of worsening symptoms in patients with mild COVID-19. Our study supports Huashibaidu granule as an active option for early treatment of mild COVID-19 in similar well-managed medical environments. Clinical Trial Registration:www.chictr.org.cn/showproj.aspx?proj=49408, identifier: ChiCTR2000029763.

Traditional Chinese Medicine in Treating Influenza: From Basic Science to Clinical Applications.

Influenza infection is a highly contagious, acute febrile respiratory disease caused by the influenza virus. Traditional Chinese Medicine (TCM) has dominated plenty of theoretical and practical approaches in the treatment of influenza. It is, therefore, important to highlight the effects of TCM in the clinical treatment of influenza and their impact on inhibiting the growth of this virus in laboratory experiments. We scrutinized existing evidence on whether TCM is effective in clinical applications. Moreover, we described the potential mechanisms of TCM against the influenza virus. Our findings provide analytical evidence that supports the effectiveness of TCM in treating influenza infections as well as their mechanisms against this virus.

Development of Rapid Advice Guidelines for the Treatment of Coronavirus Disease 2019 with Traditional Chinese Medicine.

The worldwide spread of the 2019 novel coronavirus has become a profound threat to human health. As the use of medication without established effectiveness may result in adverse health consequences, the development of evidence-based guidelines is of critical importance for the clinical management of coronavirus disease (COVID-19). This research presents methods used to develop rapid advice guidelines on treating COVID-19 with traditional Chinese medicine (TCM). We have followed the basic approach for developing WHO rapid guidelines, including preparing, developing, disseminating and updating each process. Compared with general guidelines, this rapid advice guideline is unique in formulating the body of evidence, as the available evidence for the treatment of COVID-19 with TCM is from either indirect or observational studies, clinical first-hand data together with expert experience in patients with COVID-19. Therefore, our search of evidence not only focuses on clinical studies of treating COVID-19 with TCM but also of similar diseases, such as pneumonia and influenza. Grading of recommendations assessment, development and evaluation (GRADE) methodology was adopted to rate the quality of evidence and distinguish the strength of recommendations. The overall certainty of the evidence is graded as either high, moderate, low or very low, and to give either "strong" or "weak" recommendations of each TCM therapy. The output of this paper will produce the guideline on TCM for COVID-19 and will also provide some ideas for evidence collection and synthesis in the future development of rapid guidelines for COVID-19 in TCM as well as other areas.

Chronic oxymatrine treatment induces resistance and epithelial­mesenchymal transition through targeting the long non-coding RNA MALAT1 in colorectal cancer cells.

A major reason for colorectal cancer (CRC) chemoresistance is the enhanced migration and invasion of cancer cells, such as the cell acquisition of epithelial-mesenchymal transition (EMT). Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been considered as a pro-oncogene in multiple cancers. However, the precise functional mechanism of lncRNA MALAT1 in chemoresistance and EMT is not well known. In the present study, we focused on the effect of oxymatrine on CRC cells and further investigated the role of MALAT1 in oxymatrine-induced resistance and EMT process. The human CRC cell line HT29 was exposed to increasing doses of oxymatrine to establish stable cell lines resistant to oxymatrine. The established HT29 oxymatrine resistant cells showed an EMT phenotype including specific morphologic changes, enhanced migratory and invasive capacity, and downregulation of E-cadherin protein expression. Subsequently, high-throughput HiSeq sequencing and RT-qPCR showed that lncRNA MALAT1 was significantly upregulated in the oxymatrine resistant cells (P<0.01), while knockdown of MALAT1 partially reversed the EMT phenotype in HT29 resistant cells. Furthermore, oxymatrine treatment suppressed the migration and invasion ability of CRC cells, however, this effect was significantly reversed by overexpression of MALAT1. Finally, we investigated the clinical role of MALAT1 and found that high lncRNA MALAT1 expression level is associated with poor prognosis in CRC patients receiving oxymatrine treatment (P<0.01). In conclusion, we demonstrate that lncRNA MALAT1 is a stimulator for oxymatrine resistance in CRC and it may provide therapeutic and prognostic information for CRC patients.